MicroRNAs are small, 22 nucleotide-long, non-coding RNAs that regulate gene expression via binding to the 3 UTR of target genes, which results in the suppression of protein translation and decreased mRNA stability. Here, we hypothesized that microRNAs modulate the pathogenesis of asthma. A genome wide screen of the lung microRNA transcriptome was utilized to identify microRNAs whose expression is altered in an experimental murine model of house dust mite-induced asthma. In addition, the effect of corticosteroid treatment on microRNA expression was assessed. Ongoing work is directed at generating mice that conditionally express or delete candidate microRNA genes in lung cells. We have generated a transgenic mouse that over-expresses one of the candidate microRNA genes in airway epithelial cells, which has been utilized for gain-of-function experiments to characterize its role in the pathogenesis of asthma. Ongoing studies are investigating the pathway by which this candidate microRNA modifies the manifestations of experimental house dust mite-induced asthma. In addition, we have created a conditional, cell-specific knock-out mouse for this microRNA, which will be used to confirm its role in asthma.